Abstract
Extracellular ATP plays important roles in coordinating the activities of astrocytes and neurons, and aberrant signalling is associated with neurodegenerative diseases. In rodents, ATP stimulates opening of Ca2+‐permeable channels formed by P2X receptor subunits in the plasma membrane. It is widely assumed, but not verified, that P2X receptors also evoke Ca2+ signals in human astrocytes. Here, we directly assess this hypothesis. We showed that cultured foetal cortical human astrocytes express mRNA for several P2X receptor subunits (P2X4, P2X5, P2X6) and G protein‐coupled P2Y receptors (P2Y1, P2Y2, P2Y6, P2Y11). In these astrocytes, ATP stimulated Ca2+ release from intracellular stores through IP 3 receptors and store‐operated Ca2+ entry. These responses were entirely mediated by P2Y1 and P2Y2 receptors. Agonists of P2X receptors did not evoke Ca2+ signals, and nor did ATP when Ca2+ release from intracellular stores and store‐operated Ca2+ entry were inhibited. We conclude that ATP‐evoked Ca2+ signals in cultured human foetal astrocytes are entirely mediated by P2Y1 and P2Y2 receptors, with no contribution from P2X receptors.
Highlights
Extracellular ATP plays important roles in coordinating the activities of astrocytes and neurons, and aberrant signalling is associated with neurodegenerative diseases
Our results show that cultured human foetal astrocytes express mRNA for several P2X and P2Y receptors, but the Ca2+ signals evoked by ATP are entirely mediated by P2Y1 and P2Y2 receptors
We provide the first complete quantitative analysis of mRNA expression for P2 receptors in cultured foetal human cortical astrocytes, and a comprehensive pharmacological characterization of ATP-evoked Ca2+ signals
Summary
Extracellular ATP plays important roles in coordinating the activities of astrocytes and neurons, and aberrant signalling is associated with neurodegenerative diseases. ATP stimulates opening of Ca2+-permeable channels formed by P2X receptor subunits in the plasma membrane. It is widely assumed, but not verified, that P2X receptors evoke Ca2+ signals in human astrocytes. We showed that cultured foetal cortical human astrocytes express mRNA for several P2X receptor subunits (P2X4, P2X5, P2X6) and G protein-coupled P2Y receptors (P2Y1, P2Y2, P2Y6, P2Y11). In these astrocytes, ATP stimulated Ca2+ release from intracellular stores through IP3 receptors and store-operated Ca2+ entry.
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